Optimal scaling laws for domain patterns in thin ferromagnetic films with strong perpendicular anisotropy

The topic of this thesis are magnetic domains in thin ferromagnetic films with strong perpendicular anisotropy. Our starting point is Micromagnetics, a continuum model based on the principle of minimal energy. At its core is the micromagnetic energy functional, whose local minimizer represent the stable magnetization configurations of the ferromagnetic body. Identifying a suitable thin film regime leads us to investigate a singular limit of the nonconvex and nonlocal micromagnetic energy functional. Our asymptotic analysis yields a scaling law for the typical domain size as a function of the film thickness and another material parameter. To prove an ansatz free lower bound of the energy, we extend an interpolation inequality first obtained in [26]. Moreover, we study a shape optimization problem that can be considered as a prototypical model for a single magnetic domain. We minimize the sum of the perimeter and the dipolar self-energy among subsets of R3 with prescribed volume. Upon proving that minimizers exist, we show that they are (L3-equivalent to) connected open sets with smooth boundary. We furthermore establish a scaling law for the minimal energy in terms of the prescribed volume which yields further information about the shape of minimizers

Management of elderly patients with acute promyelocytic leukemia: progress and problems

Despite substantial progress in the management and outcome of acute promyelocytic leukemia (APL) during the last decades, older age remains a prominent negative prognostic factor. The improvement of long-term stabilization and cure of older APL patients is therefore a particular challenge. Data of unselected population-based studies suggest a high rate of exclusion from clinical trials in older age. The comparison of registry and study data indicates that study patients represent a positive selection. Older APL patients seem as sensitive to therapy as younger patients. With conventional therapy, based on all-trans retinoic acid (ATRA) and chemotherapy, over 50 % of older APL patients can probably be cured. Special problems of advanced age are the high rate of early death before or during induction therapy and the high frequency of death in remission with negative influence on the outcome. Both may be related in part to a higher vulnerability against the common treatment with ATRA and chemotherapy. Alternative less toxic approaches including arsenic trioxide (ATO) with or without ATRA and combinations with gemtuzumab ozogamicin or with reduced chemotherapy can induce long-lasting remission in all stages of APL. Considering the high curative potential and the excellent tolerance of ATO in newly diagnosed and relapsed APL, older patients are probably a particular target group for a chemotherapy-free approach with ATO

Dynamic reconfiguration of cortical functional connectivity across brain states

Throughout each day, the brain displays transient changes in state, as evidenced by shifts in behavior and vigilance. While the electrophysiological correlates of brain states have been studied for some time, it remains unclear how large-scale cortico-cortical functional connectivity systematically reconfigures across states. Here, we investigate state-dependent shifts in cortical functional connectivity by recording local field potentials (LFPs) during spontaneous behavioral transitions in the ferret using chronically implanted micro-electrocorticographic (?ECoG) arrays positioned over occipital, parietal, and temporal cortical regions. To objectively classify brain state, we describe a data-driven approach that projects time-varying LFP spectral properties into brain state space. Distinct brain states displayed markedly different patterns of cross-frequency phase-amplitude coupling and inter-electrode phase synchronization across several LFP frequency bands. The largest across-state differences in functional connectivity were observed between periods of presumed slow-wave and rapid-eye-movement-sleep/active-state, which were characterized by the contrasting phenomena of cortical network fragmentation and global synchronization, respectively. Collectively, our data provide strong evidence that large-scale functional interactions in the brain dynamically reconfigure across behavioral states

Constraining the marine strontium budget with natural strontium isotope fractionations (⁸⁷Sr/⁸⁶Sr*, δ^88/86Sr) of carbonates, hydrothermal solutions and river waters

We present strontium (Sr) isotope ratios that, unlike traditional 87Sr/86Sr data, are not normalized to a fixed 88Sr/86Sr ratio of 8.375209 (defined as δ88/86Sr = 0 relative to NIST SRM 987). Instead, we correct for isotope fractionation during mass spectrometry with a 87Sr–84Sr double spike. This technique yields two independent ratios for 87Sr/86Sr and 88Sr/86Sr that are reported as (87Sr/86Sr*) and (δ88/86Sr), respectively. The difference between the traditional radiogenic (87Sr/86Sr normalized to 88Sr/86Sr = 8.375209) and the new 87Sr/86Sr* values reflect natural mass-dependent isotope fractionation. In order to constrain glacial/interglacial changes in the marine Sr budget we compare the isotope composition of modern seawater ((87Sr/86Sr*, δ88/86Sr)Seawater) and modern marine biogenic carbonates ((87Sr/86Sr*, δ88/86Sr)Carbonates) with the corresponding values of river waters ((87Sr/86Sr*, δ88/86Sr)River) and hydrothermal solutions ((87Sr/86Sr*, δ88/86Sr)HydEnd) in a triple isotope plot. The measured (87Sr/86Sr*, δ88/86Sr)River values of selected rivers that together account for not, vert, similar18% of the global Sr discharge yield a Sr flux-weighted mean of (0.7114(8), 0.315(8)‰). The average (87Sr/86Sr*, δ88/86Sr)HydEnd values for hydrothermal solutions from the Atlantic Ocean are (0.7045(5), 0.27(3)‰). In contrast, the (87Sr/86Sr*, δ88/86Sr)Carbonates values representing the marine Sr output are (0.70926(2), 0.21(2)‰). We estimate the modern Sr isotope composition of the sources at (0.7106(8), 0.310(8)‰). The difference between the estimated (87Sr/86Sr*, δ88/86Sr)input and (87Sr/86Sr*, δ88/86Sr)output values reflects isotope disequilibrium with respect to Sr inputs and outputs. In contrast to the modern ocean, isotope equilibrium between inputs and outputs during the last glacial maximum (10–30 ka before present) can be explained by invoking three times higher Sr inputs from a uniquely “glacial” source: weathering of shelf carbonates exposed at low sea levels. Our data are also consistent with the “weathering peak” hypothesis that invokes enhanced Sr inputs resulting from weathering of post-glacial exposure of abundant fine-grained material

Compact Chirped Fiber Bragg Gratings for Single-Photon Generation from Quantum Dots

A scalable source of single photons is a key constituent of an efficient quantum photonic architecture. To realize this, it is beneficial to have an ensemble of quantum emitters that can be collectively excited with high efficiency. Semiconductor quantum dots hold great potential in this context, due to their excellent photophysical properties. Spectral variability of quantum dots is commonly regarded as a drawback introduced by the fabrication method. However, this is beneficial to realize a frequency-multiplexed single-photon platform. Chirped pulse excitation, relying on the so-called adiabatic rapid passage, is the most efficient scheme to excite a quantum dot ensemble due to its immunity to individual quantum dot parameters. Yet, the existing methods of generating chirped laser pulses to excite a quantum emitter are bulky, lossy, and mechanically unstable, which severely hampers the prospects of a quantum dot photon source. Here, we present a compact, robust, and high-efficiency alternative for chirped pulse excitation of solid-state quantum emitters. Our simple plug-and-play module consists of chirped fiber Bragg gratings (CFBGs), fabricated via femtosecond inscription, to provide high values of dispersion in the near-infrared spectral range, where the quantum dots emit. We characterize and benchmark the performance of our method via chirped excitation of a GaAs quantum dot, establishing high-fidelity single-photon generation. Our highly versatile chirping module coupled to a photon source is a significant milestone toward realizing practical quantum photonic devices

Genomic Resources Notes Accepted 1 August 2014–30 September 2014

This article documents the public availability of (i) transcriptome sequence data, assembly and annotation, and single nucleotide polymorphisms ( SNP s) for the cone snail Conus miliaris ; (ii) a set of SNP markers for two biotypes from the Culex pipiens mosquito complex; (iii) transcriptome sequence data, assembly and annotation for the mountain fly Drosophila nigrosparsa ; (iv) transcriptome sequence data, assembly and annotation and SNP s for the Neotropical toads Rhinella marina and R. schneideri ; and (v) partial genomic sequence assembly and annotation for 35 spiny lizard species (Genus Sceloporus ).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110107/1/men12340-sup-0004-AppendixS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110107/2/men12340-sup-0003-AppendixS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110107/3/men12340-sup-0002-AppendixS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110107/4/men12340-sup-0005-AppendixS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110107/5/men12340.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110107/6/men12340-sup-0001-AppendixS1.pd

Monocyte-Directed RNAi Targeting CCR2 Improves Infarct Healing in Atherosclerosis-Prone Mice

Background—Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6Chigh monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E–deficient (apoE−/−) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset–targeted RNAi altered infarct inflammation and healing. Methods and Results—Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE−/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18–labeled positron emission tomography agent (18F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P<0.05), whereas 18F-FXIII positron emission tomography reflected unimpeded matrix cross-linking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29% to 35% (P<0.05). Conclusion—CCR2-targeted RNAi reduced recruitment of Ly-6Chigh monocytes, attenuated infarct inflammation, and curbed post-MI left ventricular remodeling.National Heart, Lung, and Blood InstituteUnited States. Dept. of Health and Human Services (contract No. HHSN268201000044C)National Institutes of Health (U.S.) (grant R01-HL096576)National Institutes of Health (U.S.) (grant R01-HL095629)National Institutes of Health (U.S.) (grant T32-HL094301)Deutsche Forschungsgemeinschaft (HE-6382/1-1

Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies

Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN